摘要:

The insertion/deletion (I/D) polymorphism of the ACE gene accounts for 50% of the variation in serum ACE levels and activity. However, its functional significance with regard to diabetic complications and cardiovascular disease remains controversial. To review the literature assessing the significance of ACE gene polymorphism on the initiation and progression of diabetic complications and treatment implications, a systematic review of the Medline, Pubmed and EMBASE databases was performed. Keywords were ‘diabetes mellitus’, ‘diabetic nephropathy’, ‘ACE gene polymorphism’ and ‘genotype’, for the period 1966 to August 1999.Overall, ACE gene polymorphism appears to affect the progression of diabetic nephropathy, with individuals homozygous for the deletion allele (DD) having a shorter time period from the onset of microalbuminuria to renal replacement therapy and decreased survival thereafter. This may reflect relative resistance to ACE inhibitor therapy. There is no association between ACE gene polymorphism and retinopathy. Further large prospective studies are required to clarify the association of ACE gene polymorphism and diabetic complications. However, it appears that the deletion allele acts in a co-dominant manner as a susceptibility factor in the progression of diabetic nephropathy. ACE genotyping may therefore provide a simple method of identifying high risk individuals and allow the implementation of early and aggressive therapy.

ISSN:1173-8804    

出版商:ADIS    

年代:2000

数据来源: ADIS

摘要:

HIV infection recently has been complicated by the emergence of a rare metabolic dysmorphic disorder characterised by fat atrophy, redistribution and accumulation in the setting of hyperlipidaemia and, on occasion, hyperglycaemia. The disorder, sometimes referred to as HIV-associated Adipose Redistribution Syndrome (HARS), has a prevalence rate of about 50 to 60% and seems temporally related to the advent of highly active antiretroviral therapy, especially the usage of protease inhibitors. Various studies also implicate the nucleoside analogues stavudine, didanosine and lamivudine in the pathogenesis of HARS, especially fat atrophy. It is uncertain whether the changes described in HARS represent a single syndrome or a group of related syndromes. Reports have noted differences between morphologic and metabolic changes. More recently, it has been suggested that fat atrophy and fat accumulation may also be separate entities. There are several potential pathogenic theories for HARS that implicate both protease inhibitors and nucleoside analogues as causative agents. However, long term HIV infection rather than any specific agent or class of agent may be the source. Recombinant human growth hormone (rhGH) is a mammalian cell-derived product, which has been useful in a variety of human disorders ranging from pituitary dwarfism to septic shock. It has anabolic, immunological and metabolic properties that restore normal functioning to many aberrant disease pathways. The lipolytic properties of rhGH have been especially beneficial in the diminution of localised fat accumulation in the dorsocervical area (buffalo humps) and truncal region. This has been observed in various reports where rhGH has been administered at doses of 5 to 6 mg/day in patients with HARS for periods ranging from 3 months to >2 years. Relapses after discontinuation of rhGH occurred in most patients. Adverse effects included carpal tunnel syndrome, facial swelling, arthralgias and myalgias and worsening or onset of hyperglycaemia. The small uncontrolled studies conducted to date suggest that the most notable effect of rhGH treatment is the reduction of truncal adiposity and buffalo humps and that the agent has little effect on restoring the adiposity of the appendicular muscles, buttocks or face. Although most patients with HARS have associated hyperlipidaemia, rhGH has no notable effect on serum cholesterol and triglyceride levels. However, blood glucose levels can increase and pre-existent diabetes mellitus may worsen. A short term confirmatory placebo-controlled trial in patients with HARS is urgently needed, as are comparative trials using other anabolic agents such as oxandrolone and testosterone.

ISSN:1173-8804    

出版商:ADIS    

年代:2000

数据来源: ADIS

摘要:

Overexpression of cytokines in inflamed joints plays an important role in joint inflammation and in damage to articular tissue. Biological agents aimed at specifically antagonising tumour necrosis factor (TNF) are effective in the treatment of adult rheumatoid arthritis. A recent trial of etanercept, a genetically engineered fusion protein consisting of the Fc domain of human IgG1 and the TNF receptor p75, has demonstrated that this agent is also well tolerated and effective in patients with juvenile idiopathic arthritis (JIA). Etanercept offers a promising new alternative for patients with JIA who have persistently active arthritis despite treatment with methotrexate. Further studies are needed to clarify whether etanercept is equally effective in the various onset types of JIA (oligoarthritis, polyarthritis and systemic arthritis), whether it can modify disease progression and whether it can be administered safely for long periods of time to children.

ISSN:1173-8804    

出版商:ADIS    

年代:2000

数据来源: ADIS

摘要:

One of the earliest described conditions, gout continues to plague humanity. It is characterised by the deposition of monosodium urate crystals in the joints and soft tissue. The main clinical features of gout are hyperuricaemia, acute monoarticular arthritis, tophi and chronic arthritis, along with nephrolithiasis. Gout typically occurs in middle age and more commonly in men. Asymptomatic hyperuricaemia does not require treatment. The initial attack of acute gout usually affects a single joint, often the first metatarsal phalangeal joint. Definitive diagnosis requires demonstration of urate crystals in the joint fluid. Treatment of acute gout includes nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine and corticosteroids. The most important factor in success of treatment is how quickly therapy is begun after onset of symptoms. Drug treatment of hyperuricaemia includes allopurinol, sulfinpyrazone, probenecid and benzbromarone and should be used in patients with frequent gout attacks, tophi or urate nephropathy.

ISSN:1173-8804    

出版商:ADIS    

年代:2000

数据来源: ADIS

摘要:

Recombinant hirudins have a definite role in the treatment of patients with heparin-induced thrombocytopenia (HIT). The most important adverse effects are haemorrhages and the induction of antihirudin antibodies. Major haemorrhages were not significantly increased in patients with HIT compared with a historical control group, but prospective data comparing hirudin and heparinoids such as danaparoid are lacking. The definition of the optimal method for monitoring and the availability of an antidote for hirudin would probably increase safety with this drug. To date, haemofiltration using high-flux filter systems is the only way to remove an overdosage of hirudin from the circulation. In patients with renal impairment requiring hirudin treatment, it therefore seems safer to start with a low dose that is subsequently adjusted according to the activated partial prothromboplastin time or ecarin clotting time.Even in special circumstances, such as cardiopulmonary bypass or dialysis, hirudins can be applied successfully if care is taken to monitor their effects meticulously.There are many other indications in which hirudins have shown feasibility (e.g. acute coronary syndromes) but available data preclude definite conclusions.

ISSN:1173-8804    

出版商:ADIS    

年代:2000

数据来源: ADIS

摘要:

This review examines the efficacy of photodynamic therapy in the treatment of immunological disorders. Photodynamic therapy (PDT) is a 2-step procedure. Firstly, a photosensitiser is introduced into the body, where it accumulates selectively in cells with elevated metabolism, such as cancer cells or activated cells of the immune system. Second, light is applied at a wavelength that excites the photosensitiser, producing a variety of short-lived oxygen-derived species. The effect is dependent on the doses of both photosensitiser and activating light. The mechanisms of action of PDT are multifactorial. Induction of high levels of oxidative stress results in necrotic cell death, while lower intensity oxidative stress initiates apoptosis. Sublethal doses may result in the modification of cell surface receptor expression levels and cytokine release and consequently influence cell behaviour. Immunomodulatory PDT (IPDT) utilises mainly apoptotic and sublethal doses.The studies reported here utilise verteporfin, a benzoporphyrin-derived chlorin-like photosensitiser. Veteporfin is a second generation photosensitiser, displaying rapid clearance and consequently a reduced period of skin photosensitivity compared with the first generation photosensitiser, porfimer sodium.In vivostudies showed that IPDT was effective in alleviating immunopathology in murine models of arthritis, contact hypersensitivity, experimental allergic encephalomyelitis and retention of allogeneic skin grafts. Based on these findings, early stage clinical trials with IPDT were initiated recently for the treatment of psoriasis, psoriatic arthritis and rheumatoid arthritis.While verteporfin has been the photosensitiser which pioneered IPDT, a new benzoporphyrin derivative photosensitiser, QLT0074, is under development. This has demonstrated an enhanced avidity for target cells as well as improved clearance characteristics.

ISSN:1173-8804    

出版商:ADIS    

年代:2000

数据来源: ADIS

摘要:

ObjectiveTo identify the interferon-α (IFNα) treatment protocol most suitable for patients with thalassaemia major who have chronic hepatitis C.Design and settingThis was a meta-analysis of studies in the international literature between 1990 and 1999.MethodsStudies were identified from a search of Medline and Embase, and analysed by the Mantel-Haenszel-Peto statistical method.ResultsWe identified 6 nonrandomised trials, 2 of which were controlled, that treated a total of 201 patients. Most studies used the lowest dose level (3 MIU/m2), all used a thrice-weekly regimen, and most used IFNα-2b, although the use of natural IFNα did not induce production of anti-interferon antibodies. The best sustained response and remission rates tended to be achieved with higher doses and longer cycles of IFNα.ConclusionsThe best interferon-based therapy to treat polytransfused thalassaemic patients with chronic hepatitis C is represented by the use of natural IFNα or IFNα-2b, initially at high dosages (5 to 10 MIU/m23 times weekly) for 6 months, followed by lower dosages (3 MIU/m23 times weekly) for a further 6 to 9 months.

ISSN:1173-8804    

出版商:ADIS    

年代:2000

数据来源: ADIS